tbuckley/cabot-search huggingface dataset:
Artificial Intelligence in Medicine.
Journal: Annals of Internal Medicine (1983)

In this paper we describe how we generated written explanations to 'indirect users' of a knowledge-based system in the domain of drug prescription.We call 'indirect users' the intended recipients of explanations, to distinguish them from the prescriber (the 'direct' user) who interacts with the system.The Explanation Generator was designed after several studies about indirect users' information needs and physicians' explanatory attitudes in this domain.It integrates text planning techniques with ATN-based surface generation.A double modeling component enables adapting the information content, order and style to the indirect user to whom explanation is addressed.Several examples of computer-generated texts are provided, and they are contrasted with the physicians' explanations to discuss advantages and limits of the approach adopted.
Bringing home manufacturing of medical products
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2023)

The pharmaceutical industry has a global health story to tell. Take the R21/Matrix-M malaria vaccine as an example: starting from a laboratory in the UK, it passed a phase 2 trial in Burkina Faso, was approved by authorities in Ghana, was manufactured in India, and will return to Ghana for routine immunisation programmes. Such complexity, as well as the potential fragility and inequity of the global supply chain of medical products such as drugs, vaccines, and diagnostics, was further exposed by COVID-19.
Transplantation for metastatic liver disease
Authors: Ashley Kieran Clift, Morten Hagness, Kuno Lehmann, Charles B. Rosen, Rene Adam, Vincenzo Mazzaferro, Andrea Frilling
Journal: Journal of Hepatology (2023)

The liver is a common site of metastases from many cancers, particularly those originating in the gastrointestinal tract. Liver transplantation is an uncommonly used but promising and at times controversial treatment option for neuroendocrine and colorectal liver metastases. Transplantation with meticulous patient selection has been associated with excellent long-term outcomes in individuals with neuroendocrine liver metastases, but questions remain regarding the role of transplantation in those who could also be eligible for hepatectomy, the role of neoadjuvant/adjuvant treatments in minimising recurrence, and the optimal timing of the procedure. A prospective pilot study of liver transplantation for unresectable colorectal liver metastases that reported a 5-year overall survival rate of 60% reinvigorated interest in this area following initially dismal outcomes. This has been followed by larger studies, and prospective trials are ongoing to quantify the potential benefits of liver transplantation over palliative chemotherapy. This review provides a critical summary of currently available knowledge on liver transplantation for neuroendocrine and colorectal liver metastases, and highlights avenues for further study to address gaps in the evidence base.
Machine perfusion of the liver and bioengineering
Authors: Andrea Schlegel, Hynek Mergental, Constantino Fondevila, Robert J. Porte, Peter J. Friend, Philipp Dutkowski
Journal: Journal of Hepatology (2023)

With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion – one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
Correction: Endoscopic treatment for a hematoma-mediated colon obstruction caused by acupuncture: A rare case report
Authors: Shiwei Li, Siyu Sun, Guoxin Wang
Journal: Endoscopy (2023)

Correction to: Endoscopic treatment for a hematoma-mediated colon obstruction caused by acupuncture: A rare case reportEndoscopy 2023; 55(S 01): E713-E714DOI: 10.1055/a-2078-0392
Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma
Authors: Jeayeon Park, Sung Won Chung, Yun Bin Lee, Hyunjae Shin, Moon Haeng Hur, Heejin Cho, Min Kyung Park, Jeonghwan Youk, Ji Yun Lee, Jeong-Ok Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Tae Min Kim, Jeong-Hoon Lee
Journal: Clinical and Molecular Hepatology (2023)

Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6-69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29-0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26-0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33-0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32-0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.
Efficacy of culturally adapted interventions for common mental disorders in people of Chinese descent: a systematic review and meta-analysis
Authors: Siying Li, Zhenyang Xi, Phoebe Barnett, Rob Saunders, Roz Shafran, Stephen Pilling
Journal: The Lancet Psychiatry (2023)

Evidence suggests that culturally adapted psychological interventions have some benefits in treating diverse ethnic groups. However, the effect of such cultural adaptions specifically in Chinese ethnic groups has not been thoroughly reviewed. We aimed to systematically assess the evidence for the efficacy of different cultural adaptations in treating common mental disorders in people of Chinese descent (ie, ethnic Chinese populations).In this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO, CNKI, and WANFANG to identify randomised controlled trials published in English and Chinese from database inception to March 10, 2023. We included trials of culturally adapted psychological interventions in people of Chinese descent (with at least 80% of Han Chinese descent) aged 15 years or older with a diagnosis or subthreshold symptoms of common mental disorders, including depression, anxiety disorders, and post-traumatic stress disorder. We excluded studies that included participants with severe mental disorders (eg, schizophrenia, bipolar disorder), neurodevelopmental disorders, or dementia. Study selection and data extraction were done by two independent reviewers, who extracted data for study characteristics, cultural adaptations, and summary efficacy. The primary outcome was post-intervention change in symptoms (both self-reported and clinician-rated). We used random-effects models to calculate standardised mean differences. Quality was assessed using the Cochrane risk of bias tool. The study is registered with PROSPERO (CRD42021239607).We identified 32 791 records, 67 of which were included in our meta-analysis (60 done in mainland China, four in Hong Kong, and one each in Taiwan, Australia, and the USA). We included 6199 participants (mean age 39·32 years [range 16-84]), of whom 2605 (42%) were male and 3247 (52%) were female. Culturally adapted interventions had medium effect sizes in terms of reducing both self-reported (Hedges' g 0·77 [95% CI 0·61-0·94]; I2 84%) and clinician-rated (0·75 [0·54-0·96]; 86%) symptom severity across all disorders at end of treatment, irrespective of adaptation types. We noted no difference in efficacy between culturally modified interventions and culturally specific interventions. Subgroup analyses showed considerable heterogeneity. Inadequate reporting in included studies largely restricted risk-of-bias appraisals across all domains.Psychological interventions can be transported across cultures with appropriate modifications. Adaptations to interventions can be made by modifying evidence-based interventions, or in culturally specific ways that are rooted in the sociocultural context. However, findings are limited by the insufficient reporting of interventions and cultural adaptations.None.For the Chinese translation of the abstract see Supplementary Materials section.
Major Gaps in Understanding Dietary Supplement Use in Health and Disease
Authors: Regan L. Bailey, Shinyoung Jun, Alexandra E. Cowan, Heather A. Eicher-Miller, Jaime J. Gahche, Johanna T. Dwyer, Terryl J. Hartman, Diane C. Mitchell, Rebecca A. Seguin-Fowler, Raymond J. Carroll, Janet A. Tooze
Journal: Annual Review of Nutrition (2023)

Precise dietary assessment is critical for accurate exposure classification in nutritional research, typically aimed at understanding how diet relates to health. Dietary supplement (DS) use is widespread and represents a considerable source of nutrients. However, few studies have compared the best methods to measure DSs. Our literature review on the relative validity and reproducibility of DS instruments in the United States [e.g., product inventories, questionnaires, and 24-h dietary recalls (24HR)] identified five studies that examined validity (
The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study
Authors: Weiqiu Cheng, Nadine Parker, Naz Karadag, Elise Koch, Guy Hindley, Romain Icick, Alexey Shadrin, Kevin S O’Connell, Thomas Bjella, Shahram Bahrami, Zillur Rahman, Markos Tesfaye, Piotr Jaholkowski, Linn Rødevand, Børge Holen, Trine Vik Lagerberg, Nils Eiel Steen, Srdjan Djurovic, Anders M Dale, Oleksandr Frei, Olav B Smeland, Ole A Andreassen
Journal: The Lancet Psychiatry (2023)
Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus
Authors: Tim Hundscheid, Willem P de Boode
Journal: New England Journal of Medicine (2023)

trial was designed; however, on the basis of this calculation, the trial was indeed underpowered to detect a smaller, yet clinically important, difference between the groups.As rightfully stated, the appropriate postresuscitation care in extracorporeal CPR is unknown.Therefore, the possible association between blood pressure, oxygen, or carbon dioxide goals and outcomes remains speculative.Finally, we wholeheartedly agree that our results probably represent the difficulty in the deployment of extracorporeal CPR outside of high-volume centers. 4,5
Women and non-white people among Lasker Award recipients from 1946 to 2022: cross sectional study
Authors: Jeremy W Jacobs, Lorin A Bibb, Elizabeth S Allen, Dawn C Ward, Garrett S Booth, Julie K Silver, Brian D Adkins
Journal: BMJ (2023)

To determine whether gender and racial inequities exist among Lasker Award recipients. Observational, cross sectional analysis. Population based study. Recipients of four Lasker Awards from 1946 to 2022. Gender and race (non-white categorized as racialized v white categorized as non-racialized) of all Lasker Award recipients. Personal characteristics of award recipients were categorized by four independent authors using previously established methods and consistency of categorization among authors was analyzed. Women and non-white people were thought to be underrepresented among Lasker Award recipients compared with professional degree recipients overall. Among 397 Lasker Award recipients since 1946, 92.2% (366/397) were men. Most award recipients were identified as white (95.7%, 380/397). One non-white woman was identified as having received a Lasker Award over the course of seven decades. The proportion of women among award recipients in the most recent decade (2013-22) is similar to the first decade of awards (1946-55; 15.6%, 7/45 v 12.9%, 8/62). The median timeframe from terminal degree receipt to Lasker Award conferral for all award recipients is 30 years. The proportion of women who received a Lasker Award between 2019 and 2022 (7.1%) was less than would be expected based on the proportion of life science doctorates awarded to womenin 1989 (30 years previously; 38.1%). The number of women and non-white people in academic medicine and biomedical research continues to increase, yet the proportion of women among Lasker Award recipients has not changed in more than 70 years. Additionally, time from terminal degree receipt to Lasker Award conferral does not appear to fully account for the observed inequities. These findings establish the need for further investigation of possible factors that could hinder women and non-white people from entering the pool of eligible award recipients, potentially limiting the diversification of the science and academic biomedical workforce.
Natural Targeting Potent ROS‐Eliminating Tungsten‐Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension
Authors: Hong Liu, Shuya Wang, Qiaohui Chen, Xiaoyue Ge, Huang Ning, Yanzi Guo, Di Wang, Kelong Ai, Changping Hu
Journal: Advanced Healthcare Materials (2023)

Pulmonary hypertension (PH) is a disease of pulmonary artery stenosis and blockage caused by abnormal pulmonary artery smooth muscle cells (PASMCs), with high morbidity and mortality. High levels of reactive oxygen species (ROS) in pulmonary arteries play a crucial role in inducing phenotypic switch and abnormal proliferation of PASMCs. However, antioxidants are rarely approved for the treatment of PH because of a lack of targeting and low bioavailability. In this study, the presence of an enhanced permeability and retention effect (EPR)-like effect in the pulmonary arteries of PH is revealed by tissue transmission electron microscopy (TEM). Subsequently, for the first time, tungsten-based polyoxometalate nanodots (WNDs) are developed with potent elimination of multiple ROS for efficient treatment of PH thanks to the high proportion of reduced W5+ . WNDs are effectively enriched in the pulmonary artery by intravenous injection because of the EPR-like effect of PH, and significantly prevent the abnormal proliferation of PASMCs, greatly improve the remodeling of pulmonary arteries, and ultimately improve right heart function. In conclusion, this work provides a novel and effective solution to the dilemma of targeting ROS for the treatment of PH.
A chikungunya virus–like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans
Authors: Saravanan Raju, Lucas J. Adams, James T. Earnest, Kelly Warfield, Lo Vang, James E. Crowe, Daved H. Fremont, Michael S. Diamond
Journal: Science Translational Medicine (2023)

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle–adjuvanted vaccine (PXVX0317) from samples obtained from a phase 2 clinical trial in humans (NCT03483961). Immunization with PXVX0317 induced high levels of neutralizing antibody in serum against CHIKV and circulating antigen–specific B cells up to 6 months after immunization. Monoclonal antibodies (mAbs) generated from peripheral blood B cells of three PXVX0317-vaccinated individuals on day 57 after immunization potently neutralized CHIKV infection, and a subset of these inhibited multiple related arthritogenic alphaviruses. Epitope mapping and cryo–electron microscopy defined two broadly neutralizing mAbs that uniquely bind to the apex of the B domain of the E2 glycoprotein. These results demonstrate the inhibitory breadth and activity of the human B cell response induced by the PXVX0317 vaccine against CHIKV and potentially other related alphaviruses.
Sexual dimorphism in the response to chronic circadian misalignment on a high-fat diet
Authors: Seán T. Anderson, Hu Meng, Thomas G. Brooks, Soon Yew Tang, Ronan Lordan, Arjun Sengupta, Soumyashant Nayak, Antonijo Mřela, Dimitra Sarantopoulou, Nicholas F. Lahens, Aalim Weljie, Gregory R. Grant, Frederic D. Bushman, Garret A. FitzGerald
Journal: Science Translational Medicine (2023)

Longitudinal studies associate shiftwork with cardiometabolic disorders but do not establish causation or elucidate mechanisms of disease. We developed a mouse model based on shiftwork schedules to study circadian misalignment in both sexes. Behavioral and transcriptional rhythmicity were preserved in female mice despite exposure to misalignment. Females were protected from the cardiometabolic impact of circadian misalignment on a high-fat diet seen in males. The liver transcriptome and proteome revealed discordant pathway perturbations between the sexes. Tissue-level changes were accompanied by gut microbiome dysbiosis only in male mice, biasing toward increased potential for diabetogenic branched chain amino acid production. Antibiotic ablation of the gut microbiota diminished the impact of misalignment. In the United Kingdom Biobank, females showed stronger circadian rhythmicity in activity and a lower incidence of metabolic syndrome than males among job-matched shiftworkers. Thus, we show that female mice are more resilient than males to chronic circadian misalignment and that these differences are conserved in humans.
Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging
Authors: Tanes I. Lima, Pirkka-Pekka Laurila, Martin Wohlwend, Jean David Morel, Ludger J.E. Goeminne, Hao Li, Mario Romani, Xiaoxu Li, Chang-Myung Oh, Dohyun Park, Sandra Rodríguez-López, Julijana Ivanisevic, Hector Gallart-Ayala, Barbara Crisol, Florence Delort, Sabrina Batonnet-Pichon, Leonardo R. Silveira, Lakshmi Sankabattula Pavani Veera Venkata, Anil K. Padala, Suresh Jain, Johan Auwerx
Journal: Science Translational Medicine (2023)

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that ceramide biosynthesis controls the decline in mitochondrial and protein homeostasis during muscle aging. Analysis of transcriptome datasets derived from muscle biopsies obtained from both aged individuals and patients with a diverse range of muscle disorders revealed that changes in ceramide biosynthesis, as well as disturbances in mitochondrial and protein homeostasis pathways, are prevalent features in these conditions. By performing targeted lipidomics analyses, we found that ceramides accumulated in skeletal muscle with increasing age across Caenorhabditis elegans, mice, and humans. Inhibition of serine palmitoyltransferase (SPT), the rate-limiting enzyme of the ceramide de novo synthesis, by gene silencing or by treatment with myriocin restored proteostasis and mitochondrial function in human myoblasts, in C. elegans, and in the skeletal muscles of mice during aging. Restoration of these age-related processes improved health and life span in the nematode and muscle health and fitness in mice. Collectively, our data implicate pharmacological and genetic suppression of ceramide biosynthesis as potential therapeutic approaches to delay muscle aging and to manage related proteinopathies via mitochondrial and proteostasis remodeling.
Comment on “Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice”
Authors: Yuanyuan Wang, Martin Weber, Oded Foreman, Helga Remy, Eva Zsuzsanna Mracsko, Jesse E. Hanson
Journal: Science Translational Medicine (2023)

We highlight potential issues with a Western blot assay using mouse anti-caspase-1 antibody to detect cleaved caspase-1 p20 subunit in mouse brain tissue lysates.
Clonally expanded, thyrotoxic effector CD8 <sup>+</sup> T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis
Authors: Melissa G. Lechner, Zikang Zhou, Aline T. Hoang, Nicole Huang, Jessica Ortega, Lauren N. Scott, Ho-Chung Chen, Anushi Y. Patel, Rana Yakhshi-Tafti, Kristy Kim, Willy Hugo, Pouyan Famini, Alexandra Drakaki, Antoni Ribas, Trevor E. Angell, Maureen A. Su
Journal: Science Translational Medicine (2023)

Autoimmune toxicity occurs in up to 60% of patients treated with immune checkpoint inhibitor (ICI) therapy for cancer and represents an increasing clinical challenge for expanding the use of these treatments. To date, human immunopathogenic studies of immune-related adverse events (IRAEs) have relied on sampling of circulating peripheral blood cells rather than affected tissues. Here, we directly obtained thyroid specimens from individuals with ICI-thyroiditis, one of the most common IRAEs, and compared immune infiltrates with those from individuals with spontaneous autoimmune Hashimoto’s thyroiditis (HT) or no thyroid disease. Single-cell RNA sequencing revealed a dominant, clonally expanded population of thyroid-infiltrating cytotoxic CXCR6 + CD8 + T cells (effector CD8 + T cells) present in ICI-thyroiditis but not HT or healthy controls. Furthermore, we identified a crucial role for interleukin-21 (IL-21), a cytokine secreted by intrathyroidal T follicular (T FH ) and T peripheral helper (T PH ) cells, as a driver of these thyrotoxic effector CD8 + T cells. In the presence of IL-21, human CD8 + T cells acquired the activated effector phenotype with up-regulation of the cytotoxic molecules interferon-γ (IFN-γ) and granzyme B, increased expression of the chemokine receptor CXCR6, and thyrotoxic capacity. We validated these findings in vivo using a mouse model of IRAEs and further demonstrated that genetic deletion of IL-21 signaling protected ICI-treated mice from thyroid immune infiltration. Together, these studies reveal mechanisms and candidate therapeutic targets for individuals who develop IRAEs.
Response to Comment on “Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice”
Authors: Eduardo A. Albornoz, Richard Gordon, Vinod Kumar, Avril A. B. Robertson, Kate Schroder, Trent M. Woodruff
Journal: Science Translational Medicine (2023)

We have replicated our original finding of elevated cleaved caspase-1 in mouse brains and neuroprotection by an NLRP3 inflammasome inhibitor in two mouse models of Parkinson’s disease.